Background
Temporomandibular disorders (TMD) are musculoskeletal pain conditions characterised by pain and dysfunction in the jaw-face muscles and/or the temporomandibular joint. Musculoskeletal pain conditions occurring at various locations may share pathophysiological mechanisms [
1‐
3]. Co-morbidity between TMD, headaches and neck/shoulder pain has been reported in TMD patient samples as well as in samples drawn from the general population [
4‐
10]. Low back pain, one of the most common pain conditions in humans [
11,
12], has been associated with other pains such as neck pain and headaches [
2,
13‐
15], which has been interpreted as a tendency for symptoms to cluster in some individuals [
16]. The source of these patterns is not known, but neurobiological sensitization processes [
17‐
19], genetically determined vulnerability and psychological factors [
20‐
22] are commonly given as possible explanations. Results of a 3-year prospective study showed a significantly increased risk of developing a new pain condition with presence of a pain condition at baseline [
23]. A more recent prospective study based on patients with non-painful TMD indicated a dose-response relationship between the number of pain sites at baseline (head, back, chest, stomach) and the risk of onset of dysfunctional TMD pain among women [
24]. Frequency of headaches was found to have a dose-response relationship with occurrence of musculoskeletal symptoms (e.g. pain in neck, shoulders and low back) in a Norwegian population [
7].
We have recently shown that patients with long-term spinal pain (neck, shoulder and/or low back) significantly more often have signs and symptoms of TMD than do matched controls [
25]. The associations remained statistically significant also after exclusion of those who reported jaw pain. It is not known whether co-morbidity between TMD and spinal pain occurs within the whole range of variation in symptom frequency and severity. Most analyses in this field have involved dichotomized samples, not taking variations of symptom severity into consideration. The aim of the present study was to test whether a reciprocal dose-response relation exists between frequency/severity of spinal pain and temporomandibular disorders (TMD). We tested the following null hypotheses:
1. Occurrence of frequent TMD symptoms and headaches does not differ significantly between study groups with varying frequency/severity of spinal pain.
2. Presence of frequent spinal pain does not differ significantly between study groups with varying frequency/severity of TMD symptoms.
Discussion
The present study showed a dose-response relation between frequency/severity of spinal pain and temporomandibular disorders (TMD). The pattern was evident in both directions, the prevalence of frequent TMD symptoms and headaches increasing with increasing frequency/severity of spinal pain, and the prevalence of frequent spinal pain increasing with increasing frequency/severity of TMD symptoms. The test for trends showed significant dose-response associations in both directions. The two tested null hypotheses were therefore rejected.
We have previously shown that patients with long-term spinal pain have a sevenfold risk of reporting pain and dysfunction in the jaw-face region and a fivefold risk of having clinical signs of TMD, compared with matched controls [
25]. This finding was recently supported in a cross-sectional analysis based on almost 30,000 adults in the USA [
12], indicating a strong relationship between reported spinal pain and jaw-face pain (adjusted OR: 11.3, 95% CI: 9.4–13.5). The present study shows a stepwise positive correlation between severity of spinal pain and pain and dysfunction in the jaw-face region. This dose-response-like pattern should not be interpreted as a sign of exposure and outcome. However, it strengthens previous results of an association between TMD and spinal pain and may point to common underlying biological or psychological mechanisms. It should be emphasized that the results are derived from a cross-sectional study and do not show causality. Owing to the study design we have no information about the temporal sequence of the examined disorders, an essential element in assessing causality. Studies with a prospective design have indicated that presence of a pain condition increases the risk of contracting TMD pain [
23,
24]. In a recent prospective study the risk for onset of facial pain, meeting research diagnostic criteria for TMD, was almost four times higher among adolescents with back pain at baseline, than among those without back pain [
33]. Papageorgiou et al. followed a cohort without low back pain at baseline and noted that musculoskeletal pain at other sites predicted future episodes of low back pain [
34]. These results are interesting, but so far there is no sufficient evidence to conclude that back pain precedes TMD, or vice versa. Psychological factors are often co-morbid with chronic pain conditions [
21,
35]. The temporal sequence of pain and depression is however not clear. In a review addressing this question the majority of studies indicated that depression was a consequence rather than an antecedent of pain [
36]. Longitudinal studies on these issues are therefore warranted.
It has been suggested that generalized pain (i.e. fibromyalgia) is at one end of a continuum [
37‐
39]. Vierck presents temporomandibular pain as an example of a focal pain condition where the nociceptive sensory input may contribute to development of generalized hypersensitivity and related susceptibility to further load [
40]. In line with this hypothesis one experimental study reports signs of mechanical allodynia in the hindpaw following nociceptive stimuli applied to the masseter muscle of rats [
41]. Other experimental studies have shown that perceived muscle pain intensity and distribution is influenced by the stimulation rate (temporal summation) and the number of stimulated afferents (spatial summation) [
42]. Temporal summation has been shown in TMD patients, as well as in other chronic pain conditions, suggesting a generalized hyperexcitability of the central nociceptive system [
3]. In a large population sample grouped with respect to frequency of reported headaches (< 7 days/month; 7–14 days/month; > 14 days/month) a dose-response pattern was demonstrated between headache frequency and 1-year prevalence of musculoskeletal symptoms (with locations including neck, shoulders, elbows, wrist/hands, chest/abdomen, upper back, low back, hips, knees, ankles/feet) [
7]. The contribution of input from the craniofacial nervous system in spreading pain may therefore be of significance and more experimental and clinical studies are needed.
Recent studies have shown that genetic polymorphism, with influence on the metabolism of catecholamines, is highly associated with pain sensitivity and the risk for developing TMD [
43‐
45]. Central sensitization may be one possible explanation for co-morbidity between pain conditions at different locations, as well as presence of allodynia and hyperalgesia [
17,
40]. Reflex connections between nociceptors and the fusimotor-muscle spindle system may also be involved in the pathophysiologic mechanisms related to pain and dysfunction [
46,
47].
The allocation of subjects in the present study to different spinal pain groups was based on the participants' reports of pain frequency in the questionnaire. For example, if a subject reported daily shoulder pain, but infrequent low back pain, the grouping was done according to the frequency of shoulder pain. Subjects who had been referred to a rehabilitation programme and who were on sick leave (SP-3) were considered to have more severe spinal pain than subjects with frequent pain but not on sick leave (SP-2). Symptom description in self-report questionnaires may be a limitation in a strict dose-response discussion; however, frequency as well as intensity and duration of pain and dysfunction are important variables in health care seeking behaviour [
48,
49]. Similarly, in this study, pain severity in the separate spinal pain groups demonstrates stepwise increased mean values of reported pain intensity and impact on ADL (Table
1). In the sub-sample test with symptoms of TMD as independent variable, we included none of the patients from the rehabilitation center. The severity of the TMD symptoms is reflected by the reported interference of jaw symptoms with daily living (Table
2). The formation of groups, aiming at discrete severity categories (dose), therefore seems valid also with regard to the mean intensity level and the impact of the symptoms on daily living.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
BW was the main author of the manuscript and participated in all stages throughout the work. HM was involved in the study design, interpretation of data and made critical comments on the manuscript. EE performed the statistical analysis and participated in the interpretation of data. AW acted as a supervisor and was involved in all parts of the study. All authors read and approved the final version of this paper.